Granzyme B-induced and caspase 3-dependent cleavage of gelsolin by mouse cytotoxic T cells modifies cytoskeleton dynamics
Granule-associated perforin and granzymes (gzms) are key effector molecules of cytotoxic T lymphocytes (Tc cells) and natural killer cells and play a critical role in the control of intracellular pathogens and cancer. Based on the notion that many gzms, including A, B, C, K, H, and M exhibit cytotox...
Gespeichert in:
| Hauptverfasser: | , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2010
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| In: |
The journal of biological chemistry
Year: 2010, Jahrgang: 285, Heft: 24, Pages: 18918-18927 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M109.056028 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.M109.056028 |
| Verfasserangaben: | Praxedis Martin, Julián Pardo, Natalie Schill, Lars Jöckel, Matthias Berg, Christopher J. Froelich, Reinhard Wallich, and Markus M. Simon |
MARC
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| 245 | 1 | 0 | |a Granzyme B-induced and caspase 3-dependent cleavage of gelsolin by mouse cytotoxic T cells modifies cytoskeleton dynamics |c Praxedis Martin, Julián Pardo, Natalie Schill, Lars Jöckel, Matthias Berg, Christopher J. Froelich, Reinhard Wallich, and Markus M. Simon |
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| 520 | |a Granule-associated perforin and granzymes (gzms) are key effector molecules of cytotoxic T lymphocytes (Tc cells) and natural killer cells and play a critical role in the control of intracellular pathogens and cancer. Based on the notion that many gzms, including A, B, C, K, H, and M exhibit cytotoxic activity in vitro, all gzms are believed to serve a similar function in vivo. However, more recent evidence supports the concept that gzms are not unidimensional but, rather, possess non-cytotoxic potential, including stimulation of pro-inflammatory cytokines and anti-viral activities. The present study shows that isolated mouse gzmB cleaves the actin-severing mouse protein, cytoplasmic gelsolin (c-gelsolin) in vitro. However, when delivered to intact target cells by ex vivo immune Tc cells, gzmB mediates c-gelsolin proteolysis via activation of caspases 3/7. The NH(2)-terminal c-gelsolin fragment generated by either gzmB or caspase 3 in vitro constitutively severs actin filaments without destroying the target cells. The observation that gzmB secreted by Tc cells initiates a caspase cascade that disintegrates the actin cytoskeleton in target cells suggests that this intracellular process may contribute to anti-viral host defense. | ||
| 650 | 4 | |a Animals | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Caspase 3 | |
| 650 | 4 | |a CD8-Positive T-Lymphocytes | |
| 650 | 4 | |a Cytoskeleton | |
| 650 | 4 | |a Fibroblasts | |
| 650 | 4 | |a Gelsolin | |
| 650 | 4 | |a Granzymes | |
| 650 | 4 | |a Lymphocytic choriomeningitis virus | |
| 650 | 4 | |a Mice | |
| 650 | 4 | |a Microscopy, Fluorescence | |
| 650 | 4 | |a Models, Biological | |
| 650 | 4 | |a RNA, Messenger | |
| 650 | 4 | |a T-Lymphocytes, Cytotoxic | |
| 650 | 4 | |a Transcription, Genetic | |
| 700 | 1 | |a Pardo, Julián |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schill, Natalie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Jöckel, Lars |e VerfasserIn |4 aut | |
| 700 | 1 | |a Berg, Matthias |e VerfasserIn |4 aut | |
| 700 | 1 | |a Froelich, Christopher J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wallich, Reinhard |e VerfasserIn |0 (DE-588)1059566710 |0 (DE-627)798640839 |0 (DE-576)163467781 |4 aut | |
| 700 | 1 | |a Simon, Markus M. |e VerfasserIn |4 aut | |
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